The conversion of renewable biomass resources into chemicals and fuels traditionally obtained from petroleum is strategically important to improve the sustainability of the chemical industry. Lignocellulosic biomass is the non-edible portion of biomass, and extensive research has been carried out in its conversion into platform molecules. The platform molecule 5-hydroxymethylfurfural (HMF), produced from the Brønsted acid-catalyzed dehydration of C6 sugars (hexoses), is considered to be one of the top value-added chemicals.[1, 2] Mechanistic studies have shown that HMF is formed from the dehydration of the hexoses in the furanose form (5 member ring).[2-4] Although glucose is the most abundant and least expensive hexose, it presents low amounts of furanose isomer in solution (1% in water [5]), and its dehydration into HMF thus takes place with low selectivity.[6] In contrast, fructose, which presents 21.5% of the furanose form in aqueous solution,[5] can be dehydrated to HMF in higher yields using monophasic or biphasic solvent systems, and using homogeneous and heterogeneous Brønsted acids.[7-13] Dumesic and co-workers[14, 15] employed a biphasic system consisting of an aqueous layer saturated with NaCl and containing fructose and HCl or H2SO4 as catalysts, in combination with an extracting organic layer to protect HMF from degradation reactions. Several alcohols, ketones and ethers were used as extracting organic layers, and yields for HMF as high as 70% were observed.[14, 15] In monophasic solvent systems using dimethyl sulfoxide or ionic liquids as solvents, HMF can be obtained with yields higher than 90%.[7, 11, 16] However, the separation and purification of HMF from these solvents are complicated.
While glucose can be obtained from cellulose by hydrolysis with yields of 98-100%, isomerization of glucose to fructose is economically limited to 42%, [17] requiring additional and expensive separation steps. As a consequence, the final market price of fructose is significantly higher than that of glucose. In order to obtain HMF in high yields from glucose, recent studies have aimed to use one-pot isomerization reactions to produce fructose by using a Lewis acid or Lewis base, followed by Brønsted acid-catalyzed dehydration of fructose to HMF. See Reaction Scheme 1 and FIG. 1. Reaction Scheme 1 depicts the conversion of glucose to HMF by a combined isomerization/dehydration reaction pathway. FIG. 1 is a very abbreviated reaction scheme showing how furfural and HMF can be derived from a biomass feedstock.

Zhao et al.[18] first reported HMF yields of 68-70% from glucose in the ionic liquid 1-ethyl-3-methyl-imidazolium chloride using CrCl2 as the Lewis acid catalyst. In subsequent studies with ionic liquids, HMF was produced from glucose with yields higher than 90%.[19] However, ionic liquids are not suitable for large scale applications due to their high cost and deactivation by small amounts of water.[7] Binder, et al.[12] reported that a system using dimethylacetamide (DMA), NaBr and CrCl2 resulted in HMF yields of 81%, being as effective as ionic liquid systems. Other authors have explored biphasic systems. Huang et al.[20] reported a 63% HMF yield in a biphasic reactor system with a two-step process involving the isomerization of glucose to fructose in the presence of glucose isomerase and borate ions, followed by the HCl-catalyzed dehydration of fructose to HMF. Dumesic and co-workers [6] reported 62% yield of HMF from glucose using a biphasic reactor consisting of AlCl3.6H2O and HCl as catalysts in water saturated with NaCl, in contact with sec-butylphenol. Abu-Omar et al. reported an HMF yield of 61% from glucose using AlCl3.6H2O as the catalyst in a biphasic system where THF was used as the extracting solvent [43, 44]. In all of these systems, the main goal was to maximize HMF yield, while the upgrading and purification of HMF and the sustainability of the process remained as secondary problems. For example, reutilization of homogeneous catalysts can be an issue, and these catalysts lead to corrosions problems that require expensive materials of construction. Moreover, the replacement of these homogeneous catalysts with heterogeneous catalysts is not possible in the presence of salts, due to exchange of protons on the catalyst with cations in solution, leading to deactivation of the heterogeneous catalyst.
Recent studies have shown that hydrotalcites [28] and tin containing zeolites and silicas [29] are active for glucose isomerization to fructose. Using a combination of Sn-β and HCl in a biphasic system, Nikolla et al. [30] obtained HMF yields of 57% at 79% conversion of glucose. No tin leaching was observed. Takagaki, et al. [28] reported HMF yields of 42% at 73% conversion in a two-step process by combining the solid Brønsted acid catalyst, Amberlyst-70 (Amb-70), and a solid base catalyst, hydrotalcite, in N,N-dimethylformamide.
HMF is an important chemical intermediate for a host of downstream reactions. The main reaction pathways for the production of chemicals from HMF are oxidation and hydrogenation. See FIG. 2 for a summary of exemplary reactions that can be conducted using furfural or HMF as the starting material. Hydrogenation, for example, can lead to 2,5-dihydroxymethylfuran (DHMF) or 2,5-dihydroxymethyltetrahhydrofuran (DHMTHF) (not shown in FIG. 2). Both compounds are important solvents and monomers for commercially produced polymers [41]. Additionally there has been much commercial interest in converting HMF to 2,5-furandicarboxylic acid (FDCA). FDCA can be used as a monomer or co-monomer to make fiber and packaging polyesters that compete with polyethylene terephthalate (PET). PET is a commodity polymer that ranks third in world-wide production volume, trailing only polyethylene and polypropylene. World-wide PET production was 49 million tons in 2009.[37]
Importantly, however, separating HMF from organic solvents is extremely difficult. Separating HMF from an organic solvent via distillation requires using high temperatures and/or low pressures, which can lead to degradation of HMF. Also, the high cost of separation and product losses associated with the separation process reduce the economic potential of the overall HMF process. Moreover, HMF is proposed to be a platform chemical which would be upgraded to other value-added chemicals such as 2,5-dimethylfuran (DMF), 5-hydroxymethyl-2-furancarboxylic acid (HMFCA), 2,5-diformylfuran (DFF) and 2,5-furandicarboxylic acid (FDCA). Thus, a process which integrates the upgrading of HMF along with the ease of separation of the final product from the reaction mixture is highly desirable.
The focus of the research to date on HMF production has been on optimizing yields via the judicious selection of solvents and catalysts. But there has been very little research on the feasibility and economics of separating the HMF product from the solvent and catalysts used in the production process. Similarly, there has been very little research on how to integrate the glucose-to-HMF dehydration reaction to downstream reactions to upgrade the HMF into value-added chemicals. In the literature examples mentioned above, intricate separation steps are required to recover the catalysts and the solvents. Economically speaking, the catalysts are sufficiently expensive that they must be recovered to make the processes financially viable. Even if heterogeneous catalysts are used (thus rendering recovery very simple), separating HMF from a high boiling point solvent quickly and economically is not so straightforward. Distillation at high temperatures risks polymerization of the HMF; vacuum distillation increases the cost of the purification.
One of the main drawbacks of the biphasic systems reported by date are that they rely on using salts to drive separation of the two phases and to increase the partition of the HMF into the organic phase. The use of salts in the aqueous phase complicates the use of solid catalysts because they are not long-lasting in the aqueous phase (leaching, collapse) and the acid sites are exchanged by the cation present in the salt, leading to the formation of homogeneous mineral acids. These mineral acids need to be removed from the HMF before further upgrading reactions can be conducted.
Thus, for the economic viability and environmental sustainability of the HMF production process, there is a long-felt and unmet need to produce value-added chemicals from HMF in a process that greatly simplifies or eliminates entirely the need to separate the HMF from the organic solvent in which it is produced.